► Establishes a causal link between video game play and task-switching improvements. ► Game player switch advantage seen with both manual and vocal responses. ► Game player switch advantage seen in ...both perceptual and cognitive tasks. ► Game player switch advantage seen for goal- and motor-switches.
There is now a substantial body of work demonstrating that action video game experience results in enhancements in a wide variety of perceptual skills. More recently, several groups have also demonstrated improvements in abilities that are more cognitive in nature, in particular, the ability to efficiently switch between tasks. We add to this body of work by demonstrating that the action video game player switch cost advantage generalizes to (1) vocal responses in addition to traditional manual responses, (2) tasks that are more cognitive rather than perceptual in nature, and (3) goal switches as well as motor switches. Finally, a training study establishes that the relationship between the reduction in switch cost and action game playing is causal.
Objective: While recognition memory has been the primary tool for the assessment of performance validity in neuropsychological evaluations, some consideration has also been given to embedded measures ...from other cognitive domains, including processing speed. The present study evaluated the classification accuracy of several speed-based measures in a Veterans Affairs Medical Center Polytrauma sample. Method: The present sample consisted of 114 military veterans (Mean age = 35.5, SD = 9.4) referred for a suspected history of mild traumatic brain injury who were administered a full neuropsychological protocol that included several validity checks. Veterans were assigned to Valid (n = 80) or Invalid (n = 34) groups based on outcomes of performance validity measures (PVMs). Results: Several processing speed measures yielded acceptable or excellent classification accuracy; sensitivity values ranged from 29 to 53% with specificity values above 90%. Efforts to identify an improved algorithm that would collapse across multiple processing speed PVMs were unsuccessful compared to classification based on single measures. Conclusions: Processing speed measures can serve as efficient performance validity assessment tools.
Abstract Background Previous studies have indicated that obsessive-compulsive disorder (OCD) might have a reduced placebo response compared to other anxiety-related disorders including generalized ...anxiety disorder, panic disorder, post-traumatic stress disorder, and social anxiety disorder. No previous analysis has directly compared antidepressant and placebo responses between OCD and these conditions. Method We analyzed pre-post change scores within drug and placebo groups as well as between-groups change scores (i.e., drug compared to placebo) for all FDA-approved antidepressants for the treatment of these five anxiety-related disorders. Antidepressants included duloxetine, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and venlafaxine. Random effects meta-analysis was used to examine all trials submitted to the FDA, plus additional post-approval trials available from manufacturer-sponsored clinical trial registers. Clinician-rated symptom inventories were the outcome measures for all conditions to facilitate comparisons across diagnoses. Results Fifty-six trials met inclusion criteria. OCD had significantly lower pre-post effect sizes ( p s<0.003) for both placebo (Hedges' g =0.49) and antidepressants ( g =0.84) compared to the other four conditions ( g s between 0.70 and 1.10 for placebo and 1.11 and 1.40 for antidepressants). However, the drug-placebo effect sizes did not significantly differ across diagnoses ( Q (4)=6.09, p =0.193, I 2 =34.3% 95% CI: −7.0,59.7), with g s between=0.26 and 0.39. Conclusions Overall pre-post change scores were smaller for OCD compared to other anxiety disorders for both antidepressants and placebo, although drug-placebo effects sizes did not significantly differ across disorders. Theoretical and clinical implications for the understanding and treatment of OCD are discussed.
Previous meta-analyses of published and unpublished trials indicate that antidepressants provide modest benefits compared to placebo in the treatment of depression; some have argued that these ...benefits are not clinically significant. However, these meta-analyses were based only on trials submitted for the initial FDA approval of the medication and were limited to those aimed at treating depression. Here, for the first time, we assess the efficacy of a selective serotonin reuptake inhibitor (SSRI) in the treatment of both anxiety and depression, using a complete data set of all published and unpublished trials sponsored by the manufacturer.
GlaxoSmithKline has been required to post the results for all sponsored clinical trials online, providing an opportunity to assess the efficacy of an SSRI (paroxetine) with a complete data set of all trials conducted. We examined the data from all placebo-controlled, double-blind trials of paroxetine that included change scores on the Hamilton Rating Scale for Anxiety (HRSA) and/or the Hamilton Rating Scale for Depression (HRSD). For the treatment of anxiety (k = 12), the efficacy difference between paroxetine and placebo was modest (d = 0.27), and independent of baseline severity of anxiety. Overall change in placebo-treated individuals replicated 79% of the magnitude of paroxetine response. Efficacy was superior for the treatment of panic disorder (d = 0.36) than for generalized anxiety disorder (d = 0.20). Published trials showed significantly larger drug-placebo differences than unpublished trials (d's = 0.32 and 0.17, respectively). In depression trials (k = 27), the benefit of paroxetine over placebo was consistent with previous meta-analyses of antidepressant efficacy (d = 0.32).
The available empirical evidence indicates that paroxetine provides only a modest advantage over placebo in treatment of anxiety and depression. Treatment implications are discussed.
Chronic idiopathic constipation (CIC), like other functional gastrointestinal disorders, has been associated with a high placebo response rate. However, the placebo response in randomized controlled ...trials has not been described.
We conducted a search of the medical literature following the protocol outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement using MEDLINE, EMBASE and EMBASE Classic, Web of Science, and the Cochrane Central Register of Controlled Trials for all drugs used for the treatment of CIC. Two independent reviewers performed eligibility assessment and data extraction. The mean response rate was examined for the following 2 responder endpoints: (i) greater than or equal to 3 complete spontaneous bowel movements (CSBMs)/wk (≥3 CSBMs/wk responders) and (ii) mean increase of ≥1 CSBM/wk compared with baseline (increase in ≥1 CSBM/wk responders).
A total of 23 placebo-controlled trials met our inclusion criteria and were included in this meta-analysis. The placebo response in CIC trials ranged from 4% to 44%. The magnitude of the placebo response was 13% (95% confidence interval 11%-16%) with the ≥3 CSBM/wk responder endpoint and 28% (95% confidence interval 21%-30%) with the increase of ≥1 in the CSBM responder endpoint. Higher baseline CSBM, older age, and trials with more male participants were significantly associated with a stronger placebo response for both the ≥3 CSBMs/wk endpoint and increase in the ≥1 CSBM/wk endpoint. Trial characteristics such as location (Europe vs Asia/United States) and laxative class (prokinetic vs secretagogue) revealed key differences in the placebo response for both endpoints. The placebo response was not significantly affected by the number of study visits, study duration, year of publication, number of drop outs, or likelihood of receiving active drug.
The placebo response in CIC trials ranges from 4% to 44% depending on the endpoint. Modifying factors of the placebo response include multiple subject and trial characteristics.
The objective of this study was to determine to what extent verbal fluency measures can be used as performance validity indicators during neuropsychological evaluation. Participants were clinically ...referred for neuropsychological evaluation in an urban-based Veteran's Affairs hospital. Participants were placed into 2 groups based on their objectively evaluated effort on performance validity tests (PVTs). Individuals who exhibited credible performance (n = 431) failed 0 PVTs, and those with poor effort (n = 192) failed 2 or more PVTs. All participants completed the Controlled Oral Word Association Test (COWAT) and Animals verbal fluency measures. We evaluated how well verbal fluency scores could discriminate between the 2 groups. Raw scores and T scores for Animals discriminated between the credible performance and poor-effort groups with 90% specificity and greater than 40% sensitivity. COWAT scores had lower sensitivity for detecting poor effort. A combination of FAS and Animals scores into logistic regression models yielded acceptable group classification, with 90% specificity and greater than 44% sensitivity. Verbal fluency measures can yield adequate detection of poor effort during neuropsychological evaluation. We provide suggested cut points and logistic regression models for predicting the probability of poor effort in our clinical setting and offer suggested cutoff scores to optimize sensitivity and specificity.
Longitudinal investigations are needed to improve understanding of the contributions of cerebral small vessel disease to the clinical manifestation of Alzheimer's disease, particularly in the early ...disease stages. This study leveraged the National Alzheimer's Coordinating Center Uniform Data Set to longitudinally examine the association between white matter hyperintensities and neuropsychological, neuropsychiatric, and functional decline among participants with normal cognition.
The sample included 465 participants from the National Alzheimer's Coordinating Center Uniform Data Set who had quantitated volume of white matter hyperintensities from fluid-attenuated inversion recovery MRI, had normal cognition at the time of their MRI, and were administered the National Alzheimer's Coordinating Center Uniform Data Set neuropsychological test battery within 1 year of study evaluation and had at least two post-MRI time points of clinical data. Neuropsychiatric status was assessed by the Geriatric Depression Scale-15 and Neuropsychiatric Inventory-Questionnaire. Clinical Dementia Rating Sum of Boxes defined functional status. For participants subsequently diagnosed with mild cognitive impairment (MCI) or dementia, their impairment must have been attributed to Alzheimer's disease (AD) to evaluate the relationships between WMH and the clinical presentation of AD.
Of the 465 participants, 56 converted to MCI or AD dementia (average follow-up = 5 years). Among the 465 participants, generalized estimating equations controlling for age, sex, race, education, APOE ε4, and total brain and hippocampal volume showed that higher baseline log-white matter hyperintensities predicted accelerated decline on the following neuropsychological tests in rank order of effect size: Trails B (p < 0.01), Digit Symbol Coding (p < 0.01), Logical Memory Immediate Recall (p = 0.02), Trail Making A (p < 0.01), and Semantic Fluency (p < 0.01). White matter hyperintensities predicted increases in Clinical Dementia Rating Sum of Boxes (p < 0.01) and Geriatric Depression Scale-15 scores (p = 0.01). Effect sizes were comparable to total brain and hippocampal volume. White matter hyperintensities did not predict diagnostic conversion. All effects also remained after including individuals with non-AD suspected etiologies for those who converted to MCI or dementia.
In this baseline cognitively normal sample, greater white matter hyperintensities were associated with accelerated cognitive, neuropsychiatric, and functional decline independent of traditional risk factors and MRI biomarkers for Alzheimer's disease.
We examined baseline and longitudinal associations between plasma neurofilament light (NfL) and total tau (t-tau), and the clinical presentation of Alzheimer's disease (AD). A total of 579 ...participants (238, normal cognition NC; 185, mild cognitive impairment MCI; 156, AD dementia) had baseline blood draws; 82% had follow-up evaluations. Plasma samples were analyzed for NfL and t-tau using Simoa technology. Baseline plasma NfL was higher in AD dementia than MCI (standardized mean difference = 0.55, 95% CI: 0.37–0.73) and NC (standardized mean difference = 0.68, 95% CI: 0.49–0.88), corresponded to Clinical Dementia Rating scores (OR = 1.94, 95% CI: 1.35–2.79), and correlated with all neuropsychological tests (r's = 0.13–0.42). Longitudinally, NfL did not predict diagnostic conversion but predicted decline on 3/10 neuropsychological tests. Baseline plasma t-tau was higher in AD dementia than NC with a small effect (standardized mean difference = 0.33, 95% CI: 0.10–0.57) but not MCI. t-tau did not statistically significant predict any longitudinal outcomes. Plasma NfL may be useful for the detection of AD dementia and monitoring of disease progression. In contrast, there was minimal evidence in support of plasma t-tau.
•Baseline plasma neurofilament light was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition.•Baseline plasma neurofilament light was associated with baseline cognitive test score and predicted subsequent decline but did not predict diagnostic conversion.•Baseline plasma total tau was higher in Alzheimer's disease dementia than mild cognitive impairment and normal cognition.•There were no statistically significant effects for baseline plasma total tau on cognitive decline or diagnostic conversion.
Mild cognitive impairment (MCI) is an intermediate diagnosis between normal cognition (NC) and dementia, including Alzheimer's disease (AD) dementia. However, MCI is heterogeneous; many individuals ...subsequently revert to NC while others remain stable at MCI for several years. Identifying factors associated with this diagnostic instability could assist in defining clinical populations and determining cognitive prognoses.
The current study examined whether neuropsychiatric symptoms could partially account for the temporal instability in cognitive diagnoses.
The sample included 6,763 participants from the National Alzheimer's Coordinating Center Uniform Data Set. All participants had NC at baseline, completed at least two follow-up visits (mean duration: 5.5 years), and had no recent neurological conditions. Generalized linear models estimated by generalized estimating equations examined associations between changes in cognitive diagnoses and symptoms on the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Geriatric Depression Scale (GDS-15).
1,121 participants converted from NC to MCI; 324 reverted back to NC and 242 progressed to AD dementia. Higher symptoms on the GDS-15 and circumscribed symptom domains on the NPI-Q were associated with conversion from NC to MCI and a decreased likelihood of reversion from MCI to NC. Individuals with higher symptoms on NPI-Q Hyperactivity and Mood items were more likely to progress to AD dementia.
The temporal instability of MCI can be partially explained by neuropsychiatric symptoms. Individuals with higher levels of specific symptoms are more likely to progress to AD dementia and less likely to revert to NC. Identification and treatment of these symptoms might support cognitive functioning in older adults.